Predicting regioselectivity of cytosolic SULT metabolism for drugs
This paper describes a model to predict whether a particular site on a molecule will be metabolised by cytosolic sulfotransferase enzymes (SULTs).
The earlier you catch a metabolic liability, the earlier you can design around it, minimising sunk time and cost in unnecessary synthesis and assays.
Metabolism tends to surface as one of five key questions:
- How do I design a compound with improved metabolic stability?
- Which enzymes are responsible for my compound’s metabolism?
- Which metabolites will be formed?
- How can I reduce the risk of drug-drug interactions?
- Which species will give me appropriate metabolite coverage in preclinical studies?
This guide addresses each of these questions and is written for the medicinal chemist deciding what to make next. For each of these questions, we explain why it matters for your project, what a good prediction looks like, and how you act on it.
More metabolism resources
Overcoming challenges in drug metabolism: in silico approaches
Interpreting metabolite-ID experiments; determining the right species for animal studies; providing optimisation suggestions for your medicinal chemistry colleagues to overcome…
Fast follower: optimising P450 metabolic stability
In this example we will explore the feasibility of pursuing a fast-follower for Buspirone, a 5-HT1A ligand used as an anti-anxiolytic therapeutic, which has a known liability due to rapid metabolism by CYP3A4.
